Peptides and proteins can show instability with cleavage occurring at ##STR1## bonds therein to form smaller molecules. Different theories have been advanced as to which amino acid residues are particularly likely to lead to instability, one of these identifying histidine and proline residues. Considerable problems can arise in the manufacture and storage of such compounds as a consequence of their lack of stability which can be illustrated by reference to one of the commonest of the various peptides and proteins used in therapy, insulin, which is used for the treatment of diabetes mellitus. Thus insulin can form aggregates and, although this is not of itself disadvantageous, if these undergo chemical modification so that they will not disaggregate in vivo this will have the effect of lowering the physiological activity of the insulin. Moreover, chemical modification of insulin may result in a product which is recognized by the immune system as foreign with the possibility of the development of an allergic reaction by the patient.
We have investigated a variety of chelating agents to see whether they are suitable to effect stabilization of peptide and protein materials used for therapeutic or other purposes. Surprisingly, we have found for example that whilst certain chelating agents such as ethylene diamine tetra-acetic acid and 3-hydroxy-2-methyl-4-pyrone have no stabilizing effect on insulin, and indeed can exhibit a destabilizing effect, certain other chelating agents do effect stabilization, particularly at about 4.degree. C. Such stabilization at a low temperature is of considerable importance since insulin is stored in solution form or in the freeze dried state at about 4.degree. C. prior to use or at about -10.degree. C. during various stages of manufacture and shipment of the bulk product.